Thromboembolic phenomena arising from atherosclerotic plaque in large arteries supplying the brain through the Middle Cerebral Artery (MCA) are known to account for a quarter to one-third of ischemic MCA stroke despite being one of the most treatable causes of stroke. Beyond luminal stenosis measurement, detection of atherosclerotic plaque at high-risk for causing thromboembolism, is not a part of routine stroke workup. Current plaque Magnetic Resonance Imaging (MRI) protocols, though effective, are limited by long scan times, small coverage and dependence on gadolinium contrast. Translation of plaque MRI to the clinic requires fast, large coverage, non-contrast detection of high-risk plaque features using clinically available coils. Our objective is to develop time-efficient MRI screening for detection of high-risk atherosclerotic lesions in the region supplied by the MCA. To accomplish this we will develop MRI sequences to specifically identify the three main biomarkers linked with the development of neurological symptoms: 1) intra-plaque hemorrhage and thrombus, 2) large lipid-rich necrotic core and 3) disrupted luminal surface. These sequences will be optimized for fast screening of the entire carotid artery from the arch of aorta to the base of the skull. Protocol performance will be validated against histology in patients scheduled for carotid endarterectomy. The validated protocol will then be used to test the hypothesis that ischemic stroke in the MCA territory that is not lacunar or cardiac-origin is associated with an MRI visible high-risk lesion. By demonstrating a significantly higher number of high-risk lesions on the symptomatic side than the contra-lateral side, we aim to establish the importance of screening for high-risk plaque. Our study will help to establish the prevalence of high-risk plaque in stroke attributable to large-artery disease and demonstrate the feasibility of non-contrast plaque screening in the clinical setting. Clinical use of high-risk plaque imaging may improve treatment options for stroke patients with large-artery atherosclerosis. PUBLIC HEALTH RELEVANCE: One of the major causes of stroke, the third leading cause of death in the US, is atherosclerosis of the major arteries supplying blood to the brain. Despite research advances in this area, atherosclerotic plaques at high-risk for causing stroke are not screened for in clinical stroke imaging centers. A clinically applicable imaging method for identifying high-risk plaque is developed in this proposal which, will guide clinical decision making and improve treatment strategies for these stroke patients.